Oxiranes will be used as precursors to larger oxacycles such a pyrans, oxepins, and oxocines through novel strategies that involve the rupture of the carbon-carbon bond of an epoxide. This transformation will be accomplished using several strategies, including the four-carbon ring expansion of an epoxide to an oxepin via (3,3) sigmatropic rearrangement and the homolytic bond cleavage via radical or biradical intermediates. The net effect of these transformations is the insertion of an oxygen atom into a carbon-carbon double bond. In developing these strategies there will be ample opportunity to explore reaction pathways that have not previously been exploited or possibly even observed. The long-term goal of this research project is to apply the chemistry delineated in this proposal to the synthesis of natural products of biological interest that contain medium-sized oxacycles, such as the linearly fused ring systems of the brevetoxins and the oxabicyclic skeleton of the tricothecene sesquiterpenes.